Interstitial rotating shield brachytherapy for prostate cancerQuentin E. Adams, Jinghzu Xu, Elizabeth K. Breitbach, Xing Li, Shirin A. Enger, William R. Rockey, Yusung Kim, Xiaodong Wu, and Ryan T. Flynn Citation: Medical Physics 41, 051703 (2014); doi: 10.1118/1.4870441 View online: http://dx.doi.org/10.1118/1.4870441 View Table of Contents: http://scitation.aip.org/content/aapm/journal/medphys/41/5?ver=pdfcov Published by the American Association of Physicists in Medicine Articles you may be interested in Effects of insertion speed and trocar stiffness on the accuracy of needle position for brachytherapy Med. Phys. 39, 1811 (2012); 10.1118/1.3689812 The difference of scoring dose to water or tissues in Monte Carlo dose calculations for low energy brachytherapyphoton sources Med. Phys. 38, 1526 (2011); 10.1118/1.3549760 Dosimetric optimization of a conical breast brachytherapy applicator for improved skin dose sparing Med. Phys. 37, 5665 (2010); 10.1118/1.3495539 Dose uncertainty due to computed tomography (CT) slice thickness in CT-based high dose rate brachytherapy ofthe prostate cancer Med. Phys. 31, 2543 (2004); 10.1118/1.1785454 Image-based high dose rate brachytherapy for prostate cancer Med. Phys. 31, 1309 (2004); 10.1118/1.1701953

Interstitial rotating shield brachytherapy for prostate cancerQuentin E. Adams,a) Jinghzu Xu, Elizabeth K. Breitbach, and Xing LiDepartment of Radiation Oncology, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa 52242

Shirin A. EngerMedical Physics Unit, McGill University, 1650 Cedar Ave, Montreal, Quebec H3G 1A4, Canada

William R. Rockey, Yusung Kim, Xiaodong Wu, and Ryan T. FlynnDepartment of Radiation Oncology, University of Iowa, 200 Hawkins Drive, Iowa City, Iowa 52242

(Received 5 September 2013; revised 11 March 2014; accepted for publication 23 March 2014;published 9 April 2014)

Purpose: To present a novel needle, catheter, and radiation source system for interstitial rotat-ing shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducingurethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy(HDR-BT).Methods: A wire-mounted 62 GBq 153Gd source is proposed with an encapsulated diameter of0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT nee-dle/catheter pair was constructed using concentric 50 and 75 μm thick nickel-titanium alloy (nitinol)tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535 μm thickplatinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient weregenerated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dosegradient volumes within 0–5 mm of the urethra surface were allowed to receive doses less than theprescribed dose of 100%.Results: The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axisto 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum doseto the hottest 98% of the clinical target volume (D98%), I-RSBT reduced urethral D0.1cc below that ofconventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1,3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescriptiondose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D1cc wasreduced by 7%, 6%, 6%, and 6%, respectively, and bladder D1cc was reduced by 4%, 5%, 5%, and6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq 153Gdsources.Conclusions: For the case considered, the proposed 153Gd-based I-RSBT system has the poten-tial to lower the urethral dose relative to HDR-BT by 29%–44% if the clinician allows a ure-thral dose gradient volume of 0–5 mm around the urethra to receive a dose below the prescrip-tion. A multisource approach is necessary in order to deliver the proposed 153Gd-based I-RSBTtechnique in reasonable treatment times. © 2014 American Association of Physicists in Medicine.[http://dx.doi.org/10.1118/1.4870441]

Key words: brachytherapy, rotating shield brachytherapy, intensity modulated brachytherapy

1. INTRODUCTION

Patients with localized prostate cancer are typicallytreated with external beam radiotherapy (EBRT) alone,1, 2

EBRT in combination with high-dose-rate brachytherapy(HDR-BT),3–8 EBRT in combination with low-dose-ratebrachytherapy,9 EBRT in combination with pulsed-dose-rate brachytherapy,10, 11 low-dose-rate monotherapy,12 orHDR-BT monotherapy.13, 14 Radical prostatectomy is alsoa treatment option. Radiotherapy techniques are associatedwith greater bowel toxicity than radical prostatectomy.15–19

Surgery carries a greater risk of urinary incontinence thanradiotherapy18 and possibly higher sexual dysfunctionrates.18, 19 Regardless of the treatment technique, 5-yearrelative survival rates are typically above 90%,7, 20 and

anticipated complications are important in selecting theappropriate treatment technique for prostate cancer.17–19, 21, 22

Brachytherapy techniques have been reported to providelower rectal toxicity than EBRT techniques,18 and combinedEBRT and HDR-BT have been shown to have greater lategenitourinary toxicity than EBRT alone.23 In a recent studycomparing the toxicities of localized prostate cancer patientstreated with image guided EBRT, combined EBRT and HDR-BT, and BT monotherapy it was reported that combinedEBRT and HDR-BT had the highest late (≥6 months aftertreatment) genitourinary toxicity of grade 3 or higher (4% vs12% vs 5%, p < 0.001) and ranked in the middle for lategastrointestinal toxicity of grade 2 or higher (20% vs 9% vs2%, p < 0.001).23 Of particular concern in combined EBRTand HDR-BT treatments are the grade ≥ 3 urethral stricture

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rates, which have been reported to be in the range of 7%–10%by multiple centers,4, 5, 23, 24 and of greater severity than thosefrom EBRT alone.3

Conventional interstitial HDR-BT techniques use radiationsources with dose distributions that are radially symmetricabout the catheter axis.25 Tumor dose conformity and organ-at-risk doses are sensitive to the number of catheters used,the locations of the catheters, and the tumor geometry. If itwas possible to determine the optimal number of catheters,catheter locations, and source dwell times for a given HDR-BT case, the resulting dose distribution would still onlybe optimal under the constraint that the source emits radi-ally symmetric dose distributions. Interstitial rotating shieldbrachytherapy (I-RSBT) is a novel form of high-dose-ratebrachytherapy (HDR-BT) delivered through shielded, rotat-ing catheters.26–28 I-RSBT removes the constraint that dosedistributions must be radially symmetric about each individ-ual catheter. I-RSBT thus has the potential to provide unprece-dented control over radiation dose distributions.

When I-RSBT was first conceptualized,26 specific radia-tion sources that are amenable to shielding were not identi-fied, and satisfying the need is a major challenge. Deliver-ing I-RSBT with clinically acceptable dose rates necessitatesthe development of novel radiation sources. A conventional192Ir source is not feasible for I-RSBT delivery since its radi-ation transmission, even through 1.5 mm of platinum, wouldbe about 60%. Such a high transmission was demonstrated tobe suboptimal for RSBT by Ebert in the first theoretical con-sideration of the technique,29 and such a shield is thicker thanthe thickest shield that could fit inside a 16 gauge catheter(1.651 mm diameter) while still leaving room for the radia-tion source. Low-energy brachytherapy sources such as 125Iand 103Pd, where photoelectric interactions are dominating,are attenuated strongly in tissue and are not compensated byscatter. For intermediate sources such as 153Gd, photoelectricinteractions are minimal. Attenuation in tissue is compensatedfor by scatter build up factor from low energy photons.

In this work, the 153Gd radioisotope is considered as anI-RSBT isotope with an appropriate specific activity and en-ergy spectrum to enable its use in a 16-gauge shielded nee-dle/catheter apparatus, with a similar radial dose function as192Ir.28 153Gd emits primarily intermediate-energy photons inthe 40–105 keV range, which are ideal for several reasons.First, the Compton effect is the dominant photon interac-tion in tissue for the 153Gd source, enabling straightforwardion chamber, film, and thermoluminescence dosimetry. Sec-ond, 153Gd attenuation in tissue is counteracted by single andmultiple low energy photon scatter, yielding unshielded dosedistributions with a similar radial dose function as 192Ir.28

Third, the tenth-value-layer (TVL) of 153Gd is 0.37 mm ofplatinum,28 which is small enough to enable the construc-tion of shielded catheters of 16 gauge diameter or less, en-abling safe application. Fourth, 153Gd can be produced withspecific activities high enough to enable I-RSBT treatmenttimes on the order of a few hours. Fifth, 153Gd has a half-lifeof 240 days, which is sufficiently long to reduce time- andlabor-intensive source changes relative to 192Ir, which has a74 day half-life. Sixth, mass production techniques for

153Gd are becoming available,28 creating the potential forwidespread adoption.

I-RSBT may enable both a significant reduction in ure-thral stricture rates as well as the delivery of higher prostatedose under the same healthy tissue constraints relative to con-ventional HDR-BT. As urethral dose is closely associatedwith the incidence of Grade 2 or higher acute genitourinarytoxicity,30–35 such an expectation is not unreasonable. In thecurrent work a needle, catheter, and 153Gd source apparatusfor delivering I-RSBT is defined, and the potential urethral,rectum, and bladder dose reductions of I-RSBT below con-ventional HDR-BT are investigated with a goal of the assess-ing the capability of I-RSBT to reduce urethral dose relativeto conventional HDR-BT.

2. MATERIALS AND METHODS

2.A. Source and shielded catheter design

A novel needle/catheter/source concept model system(Fig. 1) was constructed to enable I-RSBT delivery. The over-all design of the system was a dual needle system, where anapplicator allows entrance of the shielded catheter in whichthe source will be inserted. To enable this source design akey feature was the use of nitinol tubing for the needle andcatheter. Nitinol is strong, thin, and flexible, enabling theavailability of sufficient space for the rotating shield. The nee-dle is a 16-gauge nitinol tube with a wall thickness of 75 μm.The 16-gauge needle was chosen as the smallest needle gaugethat could be used with the proposed design such that thecatheter, source, and shield fit within the needle. As 15.5gauge plastic needles that are frequently used for traditionalHDR-BT have diameters greater than those that would beused for I-RSBT, 16 gauge needles are clinically reasonable.The needle contains a nitinol catheter that can rotate andtranslate freely due to the presence of 50 μm of air space be-tween the tubes. The catheter has a wall thickness of 50 μmand contains a platinum shield with a maximum thickness of535 μm and a radiotranslucent aluminum emission win-dow. The catheter contains a removable, wire-mounted, 153Gdsource. The source was modeled but not constructed, and de-signed such that the active source had a 10 mm length and a0.44 mm diameter, with a titanium encapsulation thicknessof 75 μm. The simulated 153Gd source had an activity of5550 GBq of 153Gd per gram of Gd.28 The platinum shieldwas constructed such that the 153Gd source was offset fromthe central axis of the catheter, maximizing the thickness ofthe shield under the constraint that the minimum achievablethickness of the aluminum window was 125 μm. The plat-inum shield, aluminum window, and nitinol tubing were laserbeam welded together in a 13 psi argon gas environment.

The needle would be stabilized with a stylet during inser-tion and is ultrasound, magnetic resonance, and computed to-mography imaging compatible, and sterilizable for multipleuses. Following the imaging and treatment planning process,the catheter would be inserted into the needle just prior to ra-diation delivery. During radiation delivery, the needle wouldremain stationary while the catheter is rotated and retracted.

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FIG. 1. I-RSBT 17-gauge (a) clinical concept model catheter with platinum shield (dashed line) and aluminum cap (solid line), viewing ports were cut into theneedle and catheter for demonstration purposes, (b) a 3D view of the system showing the entrance of the source into the platinum shield with the aluminumemission window, and (c) image generated from the MCNP model showing dimensions of the components and the offset position of the source within thecatheter. OD: outer diameter. ID: inner diameter.

The nitinol needle and catheter are flexible to bending mo-tion applied perpendicularly to their colinear axes, yet thecatheter’s deformation is negligible when a twisting motionis applied to the proximal catheter. This is an advantageousproperty for a catheter used for I-RSBT delivery, as it is nec-essary to ensure that catheter rotations applied outside the pa-tient result in the same rotations inside the patient.

A 153Gd source will have a substantially lower dose ratethan an 192Ir source of the same volume.28 It is expectedthat 153Gd-based I-RSBT will only be clinically feasible ifdelivered using a multisource, multicatheter approach. It isassumed in the current work that an apparatus that simul-taneously controls ten shielded 153Gd catheters for I-RSBTdelivery can be feasibly constructed and clinically imple-mented. A detailed description of such a device is beyond thescope of the current work, and a prototype system is underdevelopment.

2.B. Monte Carlo dose calculations

Dose calculations were done using the Monte Carlo N-Particle Transport Code version 5 (MCNP5), with the en-ergy deposition (F6) tally.36 The 153Gd photon spectrum wasthe same as that used by Enger et al.28 The shielded 153Gdsource was positioned at the center of a spherical water phan-tom with a density of 0.998 g/cm3 and a radius of 40 cm,which simulated an unbounded phantom.28 The source wassimulated as a pure gadolinium cylindrical active core witha length of 10 mm. The source was encapsulated by a tita-nium cylinder (ρ = 4.506 g/cm3) with a 0.59 mm outer diam-

eter, similar in outer diameter to the clinically utilized 192Irsource (VariSourceTM, Varian Medical Solution, Inc., PaloAlto, CA).37

The shield was simulated as a platinum and iridium al-loy with 90 and 10 weight percentages, respectively, a den-sity of 21.45 g/cm3, and an emission angle of 180◦. Theradio-translucent emission window was simulated as pure alu-minum with a density of 2.70 g/cm3. The needle and in-ner catheter were modeled as nitinol needles with Ni and Tiweight percentages of 55.6 and 44.4, respectively, densitiesof 6.54 g/cm3, and dimensions corresponding to a 16 gaugeneedle (outer diameter of 1.651 mm) and 17 gauge needle(outer diameter of 1.473 mm), respectively. The spaces sur-rounding the source wire and between the inner catheter andneedle were modeled as air at 760 Torr with a density of1.293 × 10−3 g/cm3. Tally cells were defined in a spheri-cal coordinate system with both the zenith (θ ) and azimuthal(ϕ) angular bin boundaries separated by 5o. The radial bin (r)boundary increments were 0.05 cm up to 3 cm away from thesource, 0.1 cm from 3 to 5 cm, 0.25 cm from 5 to 10 cm,0.5 cm from 10 to 20 cm, and 1 cm from 20 to 40 cm. Thebin boundaries had a finer resolution than those recommendedin the American Association of Physicists in Medicine TaskGroup Report 43UI,38 which recommends 10o zenith anglebin sizes and radial distances of 0.5, 1, 2, 3 and 5 cm, and7 cm for 125I.

The number of starting 153Gd photons in the simulationswas 109, which was selected such that the dose-weighted rel-ative error, σ idi/d0 was less than or equal to 0.011 for all vox-els outside of the needle. The quantity σ i is the relative error

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and di is the dose rate in tally bin i. The quantity d0 was thedose in the voxel at (θ , ϕ, r) = (90o, 0o, 1 cm), which is inthe center of the emission window on a line perpendicular tothe source axis that passes through the center of mass of theactive source.

The dose rate distribution of the unshielded 192Ir was mod-eled in MCNP5 with same radial and zenith angle bins asthe shielded 153Gd source for the purpose of calculating con-ventional HDR-BT dose distributions. The 192Ir source wasmodeled after the Varian VariSource (Varian Medical Solu-tion, Inc., Palo Alto, CA) as a pure iridium cylindrical activecore with a length of 5 mm, an active diameter of 0.34 mm,and an outer wire diameter of 0.59 mm.37 The simulated 192Irsource had an activity of 370 GBq.

2.C. Treatment planning

An anonymous prostate cancer patient was considered whowas previously treated with conventional HDR-BT. Com-puted tomography images were used for the treatment plan-ning process, and a total of 19 needles were used. The numberof rotational angles used per dwell position was 16, and thespacing between dwell positions in a given needle was 5 mm.Dose delivery was modeled in a step-and-shoot fashion,where a catheter delivers dose for a given amount of time ateach angular position for a given set of longitudinal positions.

The methods of the California Endocurietherapy Institutewere used for prostate target volume definition and treatmentplanning.39 The prostate gland was contoured and the clinicaltarget volume (CTV) was generated by adding a 5 mm marginto the prostate, but not for the prostate adjacent to the blad-der and rectum, and the proximal seminal vesicles.39 For thecase considered, the patient had a fairly average anatomy witha CTV of 60 cm3. Organs at risk were the urethra, bladder,and rectum. Dosimetric requirements were the following. Forthe CTV, 100% ≤ D90 ≤ 115%, 97% ≤ V100 ≤ 100%, V150

< 35%. In order to ensure a fair comparison between treat-ment plans, the CTV D98% was set to 100% of the prescriptiondose for all treatment plans. The D0.1cc and D1.0cc values forthe rectal wall were constrained to <85% and <80%, respec-tively, and the values for the bladder wall were constrainedto <100% and <90%, respectively. The D0.1cc and D1cc val-ues for the urethra and periapical urethra were constrained to<110% and <105%, respectively.39

The periapical urethra was considered in the treatmentplanning process since a correlation has been shown betweenprostate brachytherapy related urethral stricture and the vol-ume of the periapical urethra receiving 150% of the prescrip-tion dose (V150).40 Since the urethral and therefore periapi-cal urethral V150 is zero under the above prescription require-ments, the periapical D0.1cc% was reported instead of V150 inorder to be consistent with the dose-volume metric reportedfor the urethra.

Treatment plans for I-RSBT and HDR-BT were gener-ated using an in-house gradient-based optimizer used in pre-vious external beam radiotherapy41–43 and rotating shieldbrachytherapy44, 45 studies. The optimizer uses the linear least

squares method46 to determine the dwell time vector,⇀

t , that

TABLE I. Definitions of optimization parameters.

Parameter Definition

τ k, Tk Subset of voxel indices and number of voxels, respectively,that are inside tissue k.

d±k , β±

k Dose threshold and penalty weight, respectively, foroverdose (+) and underdose (−), for tissue k.

dV +k , V +

k , βV +k Dose threshold, percent volume threshold, and penalty

weight, respectively, for dose-volume overdose (+) fortissue k.

DV +k Difference between the dose planned and desired to V +

k inthe cumulative dose-volume histogram for tissue k.

produces the dose distribution di, for all voxels i, which iscalculated as

di =∑

j

Dij tj ,

where Dij is the dose rate at voxel i for a given source positionand direction, indexed by j. The following quadratic objectivefunction is minimized:

E(⇀

t ) =K∑

k=1

1

Tk

∑

i∈τk

[β+

k H 2(di − d+k ) + β−

k H 2(d−k − di)

+βV +k C2

(0,DV +k )

(di − dV +

k

)],

subject to the constraint that tj ≥ 0 for all j, and the opti-mization parameters are defined in Table I. The function H(x)of real number x is a Heaviside function, where H(x) = 0 if0 ≤ x and 0 otherwise, and C(a,b)(x) = x if a ≤ x ≤ b and 0 oth-erwise. The optimization parameter values used for HDR-BTand I-RSBT are listed in Table II. After each optimization wascompleted, the resulting dose distribution was scaled such that100% of the CTV received a dose of 98%.

It is expected that the shielded 153Gd radiation sources willenable substantial urethral sparing relative to conventionalHDR-BT, and that the magnitude of urethral dose reductionwill increase if the clinician allows a urethral dose gradientvolume around the urethra to receive a dose less than the pre-scription dose. The urethral dose gradient volumes consistedof the tissue between the urethra and urethral sparing margins(expansions) of 0, 1, 3, and 5 mm, inside which the dose wasallowed to drop below the prescription dose. A separate set oftreatment plans was generated using each margin.

TABLE II. Optimization parameters for I-RSBT and HDR-BT. P-Urethra isthe periapical urethra. NT is normal tissue. N/A means not applicable.

Tissue β+k d+

k β−k d−

k βV +k dV +

k V +k

CTV 0 N/A 1000 120% 0 N/A N/AUrethra 50 50% 0 N/A 0 N/A N/AP-Urethra 50 50% 0 N/A 0 N/A N/ABladder 5 50% 0 N/A 20 50% 1%Rectum 20 20% 0 N/A 20 50% 1%NT 2 80% 0 N/A 0 N/A N/A

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3. RESULTS

Monte Carlo calculated relative dose rate distributions ofthe 192Ir source and shielded 153Gd source are shown inFigs. 2(a), 2(c), 2(b), and 2(d), respectively. Anisotropywas accounted for in the dose distribution calculations. TheMCNP model was benchmarked by comparing the dose rateof a 370 GBq 192Ir source at a distance of 1 cm from the sourcecalculated from our model with the accepted 192Ir dose rate inthe literature. The results from our model gave an 192Ir doserate of 4.246 × 104 cGy h−1 which when compared with the192Ir dose rate in the literature28 of 4.184 × 104 cGy h−1, in-dicates a relative difference of less than 1.5%. The same tech-nique for calculating dose rate was used for 153Gd. The plat-inum shield reduced the dose rate on the shielded side of the153Gd source at 1 cm off-axis to 6.4% of the dose rate on theunshielded side.

Planned conventional HDR-BT and I-RSBT dose distribu-tions for a prostate cancer case are shown in Fig. 3, along withdose difference maps in which the I-RSBT dose is subtractedfrom the HDR-BT dose. Dose-volume histograms for the ure-

thral gradient margins of 0, 3, and 5 mm are shown in Fig. 4.Plots of the urethral and periapical urethral D0.1cc% percentagevariation as a function of urethral gradient margin are shownin Fig. 5(a), and the rectum and bladder D1cc percentage vari-ation as a function of urethral gradient margin are shown inFig. 5(b).

With the increasing values of urethral margin, urethralD0.1cc values and periapical urethral D0.1cc values follow adownward trend. For the case considered, for the same min-imum dose to the hottest 98% of the clinical target volume(D98%), I-RSBT reduced urethral D0.1cc below that of con-ventional HDR-BT by 29%, 33%, 38%, and 44% for urethraldose gradient volumes within 0, 1, 3, and 5 mm of the urethrasurface, respectively. Percentages are expressed relative to theprescription dose of 100%. For the same urethral dose gra-dient volumes, periapical D0.1cc was reduced by 23%, 25%,28%, and 30%, respectively, rectum D1cc was reduced by 7%,6%, 6%, and 6%, respectively, and bladder D1cc was reducedby 4%, 5%, 5%, and 6%, respectively. Increasing the urethralmargin from 0 to 5 mm for I-RSBT decreased D0.1cc for theurethra and periapical urethra by 16% and 10%, respectively,

FIG. 2. Relative dose rate distributions shown in a plane perpendicular to the source axis of (a) the 192Ir source for HDR-BT and (b) a shielded 153Gd basedI-RSBT system [Fig. 1(c)]. Relative dose rate distributions in a plane parallel to the axis of the source of (c) the 192Ir source for HDR-BT and (d) a shielded153Gd based I-RSBT system. Dose rate distributions are normalized such that the dose rate at 1 cm off-axis is 100%.

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FIG. 3. Dose distributions and dose difference maps (I-RSBT dose minus HDR-BT dose) for different urethral margins of 192Ir based HDR-BT and 153Gdbased I-RSBT sampled onto a CT scan of a prostate cancer patient.

relative to the prescription dose (Fig. 5). The urethral marginof 0 mm was included in the model in order to demonstrate therelative sparing of the urethra without a relaxed prescriptiondose constraint.

The treatment time (sum of all dwell times) to deliver 20Gy to the CTV averaged over all urethral margins using HDR-BT with a single 370 GBq 192Ir source was 12 min. For thecase considered, the treatment time (sum of all dwell times) todeliver 20 Gy to the CTV averaged over all urethral marginsusing I-RSBT with ten 62 GBq 153Gd sources was 154 min.The treatment times for each urethral margin varied by lessthan 5% from the average for HDR-BT and I-RSBT.

4. DISCUSSION

The limitations of the lower dose rate of the 153Gd sourcerelative to that of 370 GBq 192Ir source can be overcome inclinical application with the use of a multiple catheter sys-

tem. The current lack of availability of sufficient quantitiesof 153Gd required for clinical use of the 153Gd-based I-RSBTsystem is a limitation of the proposed system. However, thereare currently mass production techniques for 153Gd in devel-opment that could be used to make sufficient quantities of153Gd available for BT applications.47 As proposed, the I-RSBT approach would not have a high enough dose rate tobe considered HDR-BT, which would require a dose rate ofgreater than 12 Gy/h.45 I-RSBT would be considered mediumdose rate brachytherapy, which has a dose rate of between 1and 12 Gy/h.

The dose difference maps shown in Fig. 3 indicate that I-RSBT substantially reduced the dose to the rectum, but thedose anterior to the prostate and inferior to the bladder, par-ticularly in the pubic arch, is greater for I-RSBT than HDR-BT. The clinical implications of this dose increase are un-known, as data demonstrating complications due to increasedpubic arch dose are not available. The dose to the pubic arch

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FIG. 4. Dose-volume histograms for conventional 192Ir HDR-BT and 153Gd based I-RSBT system for urethral margins of (a) 0 mm, (b) 1 mm, (c) 3 mm, and(d) 5 mm. P. Urethra: periapical urethra.

delivered with I-RSBT will be patient-dependent, and furtherstudies with more patients are needed in order to determinethe range of expected doses. One potentially effective ap-proach is to include the pubic arch as an avoidance structurein the treatment plan optimization process.

There are several considerations that make a 2–3 h deliv-ery feasible for I-RSBT. First, conventional HDR-BT is oftendelivered on multiple days in which multiple deliveries aredone per day,3, 5–7, 23, 24, 30, 48–50 with a single needle implant.In such cases, it is not infrequent for patients to spend 12 hin the clinic for ultrasound-guided needle implantation, CTscan acquisition, treatment planning, delivery, and wait timebetween deliveries. HDR-BT patients may have an overnighthospital stay with the needles implanted. With the I-RSBTapproach, patients can spend a similar amount of time in theclinic with needles implanted, but a greater percentage of thattime would be used for the radiation delivery process. Timespent in the clinic for single-fraction I-RSBT may be morethan for conventional single-fraction HDR-BT, but still nolonger than conventional multifraction HDR-BT. If compli-cations can be reduced by using the I-RSBT approach, then itmay be desirable for patients to undergo such a procedure andspend an additional few hours under treatment. The effects offractionation in high-dose-rate brachytherapy may provide a

therapeutic advantage, and caution should be exercised whendefining clinical trials evaluating I-RSBT to ensure that the ef-fectiveness of HDR-BT at controlling disease is not sacrificedfor the sake of reducing toxicity. Third, the 153Gd gamma raysrequire far less room shielding than 192Ir gamma rays,28 andit is possible that patients could be treated in modified proce-dure rooms rather than in HDR-BT suites, and the concernsregarding facility usage that would accompany a long HDR-BT treatment may not be present with I-RSBT.

Quality assurance will be important for I-RSBT. As theshield-containing catheters are designed to move inside theneedles freely, without moving the needles, concerns regard-ing needle shift during treatment will be the same as thosefor conventional HDR-BT. The delivery system for I-RSBThas not yet been developed, therefore it is not possible atthis time to provide an in-depth explanation of the quality as-surance for the I-RSBT system. Justifying the developmentof a full I-RSBT delivery system, including quality assur-ance processes, requires establishment of dosimetric and clin-ical delivery expectations, which is the subject of the currentwork.

An important consideration when designing the model forI-RSBT was the source design, as variables such as sourcelength and diameter can have a large effect on the resulting

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FIG. 5. (a) Variation in D0.1cc (%) of urethra and periapical urethra with urethral margin and (b) variation in D1cc (%) of bladder and rectum with urethralmargin. P. Urethra: periapical urethra.

dose distributions. The 10 mm length of the source was a de-sign decision based on currently clinically utilized sources,Sources with a length of 10 mm have been used previously inVarian VariSource designs37 modeling the 153Gd as a 10 mmsource was appropriate. The 10 mm source length was chosen,as compared to a shorter source length, because it minimizedtreatment times for I-RSBT delivery.

An additional parameter considered that can alter treat-ment times and possibly improve dose distributions was theshield emission angle. Although this concept was not consid-ered in the current work, it is possible that catheters with anumber of different shield emission angles could be used dur-ing a single I-RSBT delivery. Such an approach could possi-bly improve healthy tissue sparing without loss of CTV D98%

while reducing treatment time. A similar approach has beenconsidered for intracavitary RSBT and could be extended to I-

RSBT.45 Another approach for decreasing I-RSBT treatmenttimes is to use a combination of 192Ir and shielded 153Gdsources. The 192Ir sources can be used at the periphery ofthe prostate and the shielded sources could be used close tothe urethra. The trade-offs between normal tissue sparing andtreatment time using this approach are not yet well under-stood, however, and require further consideration.

In this treatment planning study, it cannot be claimed thatthe catheter numbers and arrangements for the HDR-BT andI-RSBT sources are optimal for the sources considered. Thepositions considered were consistent for both I-RSBT andHDR-BT and they were clinically realistic. Alternative ar-rangements could be appropriate, and developing an algo-rithm for determining the optimal catheter positions for I-RSBT is a challenging optimization problem that was beyondthe scope of the current work.

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The uncertainty associated with the angular position of thesource is not yet clear, as it will depend on the I-RSBT deliv-ery method, angular accuracy of any motors involved, and theaccuracy with which a feedback-based control system for an-gular position monitoring can detect and correct for deviationsfrom the intended positions. The dosimetric impact of the po-sitional uncertainty will depend upon optimization techniqueused to generate the dwell times for each source position andshield angle, as dwell times that are smoothly varying willproduce dose distributions that are more robust with respectto positional uncertainties. It is expected that such uncertain-ties will have the greatest undesirable impact if they cause un-expected cold spots in the prostate or if they cause increasesin the dose delivered to the urethra, bladder, and/or rectumthan planned, which could result in a worse toxicity thanexpected.

The rectum and bladder D1cc values for I-RSBT were notreduced relative to HDR-BT as much as the urethral and pe-riapical urethral D0.1cc values. Rectal dose can be further re-duced by injecting hyaluronic acid51 or SpaceOARTM hydro-gel (Augmenix, Inc., Waltham, MA) into the anterior perirec-tal fat, increasing the distance between the rectum and theprostate. Such approaches may be effective if the clinical goalof I-RSBT delivery is to escalate CTV dose under normal tis-sue constraints, although the bladder dose must still be con-sidered in this process. Reducing the anterior-superior CTVdose to keep bladder dose below the constrained value maybe necessary to enable dose escalation that takes full advan-tage of the urethral sparing benefits of I-RSBT.

In addition to the benefits of the proposed system in patienttreatment, the incorporation of proximal and distal platinumcaps onto the ends of the shield, shown in Fig. 1(a), enable thecatheters to be safely retracted into a shielded container forstorage, reducing clinical staff dose due to radiation releasedalong the longitudinal axis of the source.

An alternative source considered for I-RSBT delivery was57Co.52 The advantages of 57Co over 153Gd are both a higherspecific activity and a slightly longer half-life of 271 days.However, 153Gd was chosen over the 57Co source because ofits thinner photon tenth-value layer in platinum (0.37 mm for153Gd compared to 0.7 mm for 57Co), which allows a largersource to be used in the same gauge of catheter, and a substan-tially lower cost per GBq of 153Gd compared to 57Co. Becausethe lower dose rate provided by 153Gd as a result of its lowerspecific activity can be overcome by using multiple sources,and the difference in half-lives is unlikely to affect the clin-ical feasibility of 153Gd, it was determined that 153Gd-basedsystem was the preferred source for I-RSBT treatment.28

5. CONCLUSIONS

The proposed 153Gd-based I-RSBT system has the po-tential to reduce urethral and rectal doses relative to con-ventional techniques. For the case considered, the proposed153Gd-based I-RSBT system has the potential to lower theurethral dose relative to HDR-BT by 29%–44% if the clini-cian allows a urethral dose gradient volume of 0–5 mm aroundthe urethra to receive a dose below the prescription. A multi-

source approach is necessary in order to deliver the proposed153Gd-based I-RSBT technique in reasonable treatment times.

ACKNOWLEDGMENTS

The authors thank Julie Raffi, M.S., for providing theMCNP model for the Varian VariSource. The authors aregrateful to the Carver College of Medicine Medical StudentResearch Fellowship, which funded Q.E.A. and E.K.B. Theauthors acknowledge funding from the Iowa Center for Re-search by Undergraduates for the support of J.X. and fundingfrom the Iowa Centers for Enterprise GAP Fund Program forthe support of X.L.

a)Author to whom correspondence should be addressed. Electronic mail:quentin-adams@uiowa.edu

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